Toward the Identification of Neurodevelopmental Risk Markers of Bipolar Disorder

描述（由申请人提供）：拟议的K01提案的教育目的是允许申请人接受发育情感神经科学和儿科双相情感障碍方面的培训，并获得必要的技能，以表征具有双相情感障碍高遗传风险的年轻青少年情绪调节神经系统的神经发育异常。双相情感障碍是一种慢性衰弱性精神疾病，常见于成人，儿童和青少年更是如此。它的特征是情绪调节的显著损伤，这与前额叶和皮层下神经区域的功能异常有关。双相情感障碍可能由这些神经区域的神经发育异常介导。双相情感障碍的发病在青春期急剧增加，青春期是调节和调节情绪的前额叶系统发育的关键时期。对患有双相情感障碍的父母的青少年后代的研究有望帮助阐明与双相情感障碍发展有关的一些神经机制。本研究将利用功能磁共振成像（fMRI）研究双相情感障碍遗传风险高的健康青少年与低风险对照组相比，与内隐情绪信息加工和情绪认知控制相关的神经活动的差异。第二个目标是探索这些神经活动的差异在多大程度上与青春期成熟有关。该项目的中心原则是，通过高阶认知控制过程减少情绪信息处理的调节是双相情感障碍的一个关键风险因素。这个项目补充了拟议的职业发展计划，该计划将包括获得下列方面的培训：1)研究青少年情绪调节的发育情感神经科学方法，2)与儿童双相情感障碍相关的临床问题，3)用于检查情绪调节神经系统的方法，包括认知控制和情感界面神经系统的功能磁共振成像的知识和技能的增加，以及与儿童神经影像学相关的伦理问题，4)纵向研究的设计和方法，以及模拟神经发育轨迹的先进统计技术。本研究结果将有助于识别双相情感障碍的潜在神经发育风险标志物，建立双相情感障碍特有的内表型，从而促进早期干预策略的制定。

DESCRIPTION (provided by applicant): The educational aim of the proposed K01 proposal is to allow the applicant to train in developmental affective neuroscience and pediatric bipolar disorder and acquire the skills necessary to characterize neurodevelopmental abnormalities in neural systems of emotion regulation in young adolescents at high genetic risk of bipolar disorder. Bipolar disorder is a chronic and debilitating psychiatric disorder in adults and even more so in children and adolescents. It is characterized by significant impairments in emotion regulation, which have been associated with functional abnormalities in prefrontal and subcortical neural regions. Bipolar disorder may be mediated by neurodevelopmental abnormalities in these neural regions. The onset of bipolar disorder increases dramatically in adolescence, which is a key period for the development of prefrontal systems involved in modulating and regulating emotions. Studies in adolescent offspring of parents with bipolar disorder, who are significantly at risk of developing the illness, promise to help elucidate some of the neural mechanisms involved in the development of bipolar disorder. This proposal will use functional magnetic resonance imaging (fMRI) to investigate differences in neural activity associated with implicit emotional information processing and emotional cognitive control in young healthy adolescents at high genetic risk of bipolar disorder compared to low-risk controls. The secondary goal is to explore to what extent these differences in neural activity are associated with pubertal maturation. The central tenet of the proposed project is that reduced modulation of emotional information processing by higher-order cognitive control processes represents a key risk factor for bipolar disorder. This project complements the proposed career development plan that will involve obtaining training in: 1) developmental affective neuroscience approaches to the study of emotion regulation in adolescence, 2) clinical issues associated with pediatric bipolar disorder, 3) methodology used to examine neural systems of emotion regulation, including increased knowledge and skills in fMRI of neural systems at the interface of cognitive control and emotion and ethical issues associated with pediatric neuroimaging, 4) design and methods used in longitudinal research and advanced statistical techniques for modeling neurodevelopmental trajectories. Findings from this study will contribute to identifying potential neurodevelopmental risk markers for bipolar disorder and establishing endophenotypes of emotion dysregulation specific to bipolar disorder, which will facilitate the development of early intervention strategies.